1. You may be one of several clients/customers of the CMO.
2. Your production may not command the highest priority of the CMO.
3. You may have to “compete” for production time and schedule.
4. The CMO may not be as motivated as you to achieve process optimization and realize cost savings.
5. Proximity of the CMO to your headquarters location may not allow for the same direct and frequent contact with manufacturing as you would have with a captive facility.
6. Since the sponsor company does not usually participate in the selection and hiring of the CMO managers and technicians, issues of personal chemistry and compatibility could arise.

For all of the above reasons and more, it is incumbent upon sponsor companies to provide the appropriate management and oversight of the CMO to make sure that everything is being done in their best interests.  Many virtual, start-up companies who choose to use CMO for their production employ the use of experienced consultants/contractors for this requirement rather than hire a Full-time Equivalent Employee (FTE) with this specialization.  In addition to handling the myriad of issues related to a successful validation and start-up of commercial production at a CMO, the experienced CMO manager can establish the appropriate business processes and oversight at the CMO on an ongoing basis.  Some of the things that you might want to consider are the monitoring of regular production batches.  You may not need the ‘man-in-the-plant’ to monitor each batch.  Depending on the level of technical sophistication of the CMO, some offer password protected monitoring of the sponsor’s batches on-line with actual screen views of their Manufacturing Execution System (MES) for the sponsors’ products.  If you desire to be present for production, those CMO’s who are practiced with the contract manufacturing business model, often provide visitor offices or cubicles with either hard-wired internet connectivity or wireless capability inside the facility.  You may want to have the CMO manager prepare a ‘dashboard’ of key performance metrics that the CMO is required to populate on a regular basis.  And lastly, you may want to request periodic, monthly or quarterly typically, face-to-face operational review meetings with key personnel from both sides at the CMO site.  At these meetings you can review those key performance metrics such as: productivity, quality, cost, safety, environmental, and any other regulatory interactions related to contractual accountability and compliance.

A successful contract negotiation, technical transfer, and commercial production start-up does not necessarily insure continued success over the term of the CMO Supply Agreement.  Prudent and competent ongoing management and oversight is necessary along the way.  Global BioDevelopment has competent and experienced CMO experts who can help you navigate through the uncertain waters that may await you when you make the decision to utilize a CMO.  Give Global BDI a call or e-mail and let’s have a conversation about how we can assist you with your drug supply requirements and the use of CMO.

One of the first steps in the start-up process is the preparation of and hand-off of the Technical Transfer Package (TTP) to the CMO.  Some of the typical components contained in a TTP are: the process description, the Bill of Materials (BOM), QA/QC forms, test methods and assays, toxicology data, and more.  Some sponsor companies may have well defined processes that have been developed and refined in their own small-scale facilities or pilot plants.  Others may only have a rough back-of-the-envelope process flow sketch.  In the former case, the sponsor company may just want the CMO to execute on the sponsor’s own Master Batch Record (MBR).  In the latter situation, the CMO will be expected to generate the process that best fits their facilities and unit operations.  It should be noted that the legal and cost responsibilities of the two above cases are different and should be differentiated accordingly in the contract or Supply Agreement.  Additionally, how much hands-on involvement the sponsor company chooses to have in this preparatory phase also has possible legal and contractual implications.  For example, if the sponsor company chooses heavy involvement such as co-signing almost all documents generated by the CMO, including SOP’s, then there is more of a shared responsibility for any negative outcomes in the manufacture of the API or drug product.

Moving into the pre-validation phase of the start-up process, you will probably want to produce one or more placebo or engineering batches without consuming costly active ingredients.  The protocols for these batches should be reviewed and signed off by the sponsor company.  These batches serve to confirm the operational capability or OQ of the typical IQ, OQ, PQ process within the CMO facility.  The final step before initiation of commercial production is the PQ step which usually means production of three consecutive validation batches close to the scale of commercial production.  When all three of these consecutive batches meet the finished product specifications, they may also be used for commercial launch material.  The test results from these batches are critical as well to the qualification of the CMO relative to the Pre-Approval Inspection (PAI).  The sponsor company will definitely want to have their representatives, either employees or contractors/consultants present in the plant for the above critical steps.  Following the process steps described above are just a few of the things that you can do to ensure a successful start-up at your CMO.  In Part II I’ll discuss some of the things that you should consider in managing your products manufacturing at the CMO on a continuing basis.

Global BioDevelopment has the technical expertise and competency to assist you to achieve a successful implementation of manufacturing at your CMO.  Our experienced partners can provide everything you need from process development; CM & C section preparation, technical transfer, supply agreement negotiation, and ‘man-in-the-plant’ representation for start-up and ongoing manufacturing at the CMO.

Give Global BDI a call (813-448-3093) or e-mail (info@GlobalBDI.com) and let’s have a conversation about how we can assist you with your drug supply requirements and the use of CMO.

It is not too soon to choose the CMO even in the pre-clinical phase of the drug development process, since eventually the clinical supplies will have to be manufactured in a GMP facility. Experience indicates that CMO selection, supply agreement execution, and technology transfer can take up to a year and sometimes longer. It also can preclude duplication of effort if the CMO selected has the capacity to produce the clinical supplies as well as commercial quantities for at least the first few years after product launch.

The path from drug discovery to commercialization is fraught with many risks; financial, technical, and regulatory. The employment of CMO carries its own risks and requires competent oversight and management by the sponsor company. The selection process is critical and the most important factors to consider are: Quality, Technical Competence, Timeliness, Cost, Communications, and Regulatory Compliance. It is important to note that cost should not necessarily be the overriding criterion.

As an expansion of its existing services to small companies in the drug development process, Global BioDevelopment has recently added an experienced partner for CMO implementation and even broader Supply Chain Management. Global BDI can now assist you with the identification, due diligence, auditing, and supply agreement negotiations to select the best CMO to fulfill your requirements for pre-clinical supplies to commercial launch quantities. After CMO implementation, our staff can also provide a ‘man-in-the-plant’ to oversee the critical registration and validation batches, and even periodic monitoring of commercial batches and operational performance of the CMO. Give Global BDI a call, e-mail, or FAX, and let’s have a conversation about how we can assist you with your drug supply requirements and the use of CMO.

Source: San Francisco Business Times

Source: Dow Jones Newswires

• Be able to present to potential investors a succinct 10-15 slide presentation (with more detailed slides for each section to be used as backups in an appendix) that describes.
• The opportunity and how it’s better than current therapies or emerging competition.
• The management team and its demonstrated ability to deliver timely milestones and increased company valuations.
• The required amount of funding to accomplish well-defined milestones and their justification.
• Build small but strong panels of scientific and medical experts in your therapeutic area that can advise your management team, the company’s scientific founders and Board of Directors.
• Seek advice on how to realistically calculate a “pre-money” valuation of your company that you’ll need when sufficient interest has generated term-sheets ready to be negotiated.

When all the above are in place produce a succinct one- or two-pager outlining the opportunity, the technology, the management team and the required funds to achieve important inflection points in valuation in a well-defined timeframe, and send it to potential investors whom you know or to whom you can obtain introductions via colleagues etc and ask for a face-to-face meeting.

Of particular interest to oncology researchers are the 23 categories of fundable projects related to various facets of cancer detection and treatment.  This section begins on Page 38 of the document which can be obtained by clicking on the link below.

http://grants.nih.gov/grants/funding/SBIRContract/PHS2010-1.pdf

Global BDI provides expert assistance for non-US citizens/companies interacting with the FDA. For more information, please contact us at info@globalbdi.com.

“The evaluation of abuse liability should be considered for drugs that are distributed into the brain and produce central nervous system activity, regardless of therapeutic indication. Nonclinical studies should support the design of clinical evaluations of abuse potential, classification/scheduling by regulatory agencies, and drug labeling.”  –http://www.emea.europa.eu/pdfs/human/ich/028695endraft.pdf

From our experience these current guidelines would not only apply to NCEs for human use but also for veterinary use where there is potential for the drug to cross the animal’s blood-brain barrier. For example, veterinary anesthetics may be required to be evaluated in dependency studies to assess their potential for human abuse.

Global BDI has expert consultants and laboratory capabilities to perform abuse liability testing. We conduct drug self-administration and drug-discrimination studies in rodents and non-human primates.